An Overview of Diabetic Peripheral Neuropathy

Diabetic Nerve Pain

Over time, high levels of blood glucose can damage nerve fibers, resulting in diabetic nerve pain. According to estimates, over 50% of patients with diabetes will develop nerve damage over the course of their disease. Depending on the affected nerves and severity of damage, diabetic neuropathy pain can range from mild to disabling, and in some cases, be fatal. Click through the slides to learn about how to assess and treat your patients with diabetic peripheral neuropathy, then take our quiz to test your knowledge.

The Neuropathy Spectrum

There are 4 main types of diabetic neuropathy: peripheral, autonomic, radiculoplexus, and mononeuropathy. Diabetic peripheral neuropathy is the most common, and is associated with tingling and burning sensations in the extremities. Autonomic neuropathy can disrupt the function of other organs, leading to bladder problems, constipation, sexual dysfunction, and the loss of the ability to regulate body temperature, blood pressure, and heart rate. Mononeuropathy is often the cause behind facial paralysis and problems with eyesight, though these symptoms tend to not be long-term.

Risk Factors

The risk for nerve damage from diabetes increases with the amount of time a patient has diabetes, especially if their blood glucose is not well-controlled during that time. Patients who are overweight (BMI > 24), who smoke, and who have kidney disease are also at an increased risk for nerve damage associated with diabetes. Previous studies have shown that diabetic nerve pain is also present in some patients who are prediabetic and have metabolic syndrome.

Symptoms of Diabetic Peripheral Neuropathy

A patient who has diabetic nerve pain may complain of tingling, numbness, burning, and/or general pain sensations in their feet and legs, as well as other extremities such as their hands. A patient may notice a reduced ability to feel pain or temperature change, while others may note a hypersensitivity to touch, in which even the weight of a bed sheet can cause severe pain. Other patients may notice increased muscle weakness, a loss of reflexes, especially in the ankle, and declining balance and coordination.

Disease Etiology

With over 100 known types of peripheral neuropathy, the pathophysiology of this disease is not quite clear. While many types of neuropathy are acquired from other diseases or injury, some are inherited or caused by genetic mutations. Voltage-gated sodium channels have been implicated in many forms of neuropathy, including DPN, which some research suggests is not a direct complication of diabetes, but rather a result of mutations at the Nav1.7 sodium channel.

Assessment

When a patient’s symptoms point towards DPN, it’s important to conduct a thorough medical history and physical exam to assess muscle strength and tone, tendon reflexes, and sensitivity to touch, temperature, and vibration. You may want to utilize a monofilament test to assess sensitivity to touch, while electromyography can help assess discrepancies in nerve conduction. Additionally, it is imperative that patients with diabetes undergo a comprehensive foot exam annually to assess the skin and musculoskeletal health of the feet as well as evaluate sensitivity. Feet should be thoroughly examined for sores, cracked skin, calluses, and blisters that are not healing normally in order to prevent further complications.

Treatment: Pharmacotherapy

With no treatments available to reverse the nerve fiber damage that contributes to DPN, current treatment focuses on slowing disease progression, pain management, and managing complications. There are currently 3 therapies approved by the FDA to treat the pain associated with DPN, which include pregabalin, duloxetine, and tapentadol, however gabapentin, fluoxetine, and amitriptyline have also been used as first-line therapy. Tricyclic antidepressants and SNRIs may also be prescribed to relieve pain. When prescribing any of these therapies, comorbidities and drug interactions should always be considered.

Treatment: Lifestyle Changes

More strict control of blood glucose levels can, in some cases, prevent or delay the progression of DPN and may help improve symptoms. Generally, patients with diabetes who are aged 59 and younger and who have no other medical conditions should have a target blood glucose level between 80-120 mg/dL; patients aged 60 and older, or those with other medical conditions, should have a target blood glucose level between 100-140 mg/dL. Patients should be advised to maintain a regimen of physical activity and a healthy diet plan to help reach or maintain a healthy weight. Those who smoke should receive smoking cessation support, and patients should be encouraged to avoid alcohol or drink it in moderation.

Treatment: Alternative Medicine

Several alternative therapies and treatments have been shown to improve pain in DPN, including topical capsaicin, transcutaneous electrical nerve stimulation (TENS) therapy, and acupuncture. When combined with drug therapy, these treatments may help patients reach a greater state of pain relief.

Treatment: In the Pipeline

Researchers have also reported a possible benefit from other alternative treatments, including low-dose gene therapy, botulinum toxin-A injection, and medical marijuana. In a study published in Annals of Clinical and Translational Neurology, 48% of participants who received two low-dose rounds of non-viral gene therapy VM202, which contains human hepatocyte growth factor, experienced at least a 50% reduction in pain, and also saw improved ability to perceive light touch.